The overall objectives of this research are to develop new integrated liquid chromatograph-mass spectrometer systems and to demonstrate that these new LC-MS systems provide practical solutions to difficult analytical problems of biomedical importance. Earlier work supported by this grant has led to the successful development of new practical LC-MS systems suitable foruse with nonvolatile samples and aqueous mobile phases, and a new soft ionization technique was discovered which is compatible with on-line LC-MS. In the continuation of this work we propose to further develop and refine the LC-MS techniques originating from our earlier work, to further develop and test universal LC detectors based on thenew "thermospray" vaporization and ionization process, to develop a new combination of liquid chromatography with tandem photodissociation mass spectrometry (LC-MS-PD-MS), and to apply these new techniques to important biomedical problems.